Absence of interstitial lung disease at initial visit may predict a favorable outcome for Japanese patients with systemic sclerosis with anti-topoisomerase I antibody.

Interstitial lung disease (ILD) is recognized a prognostic factor and leading cause of death in patients with systemic sclerosis (SSc). The aim of the present study is to clarify factors at an initial visit that are associated with the deterioration of ILD in SSc patients with anti-topoisomerase I (anti-topo I) antibodies. This was a single-center, retrospective, observational study. Fifty-three consecutive SSc patients with anti-topo I antibodies were included in this study. Of the 53 patients, 43 had ILD at their initial visit, whereas 10 did not. We examined the clinical and immunological factors at an initial visit that were associated with the deterioration of ILD. The deterioration of ILD was defined as the administration of intravenous cyclophosphamide (IVCY) therapy. In this cohort, 45 (85%) patients had ILD at the time of the final observation, and only two who did not have ILD at their initial visit developed ILD during the follow-up period. Until the final observation, 26 (49%) patients received IVCY therapy for the progression of ILD. The age at onset, disease duration, SSc subtype, and skin score were similar between patients with and those without IVCY therapy. Approximately 60% (26 of 43) of patients with ILD at their initial visit received IVCY therapy. On the other hand, none of the 10 patients without ILD at their initial visit received IVCY therapy. Our multivariate analyses using Cox proportional hazards regression model revealed that the presence of ILD at an initial visit was an independent factor associated with the introduction of IVCY therapy (odds ratio, 2.8e+7 [95% confidence interval, 1.8e+17-uncalculated], p = 0.0048). Although anti-topo I antibodies are strongly associated with ILD, it was unlikely for SSc patients with anti-topo I antibodies to receive IVCY therapy when they did not have ILD at an initial visit.

Total synthesis of highly oxygenated phomopsol B via acid-induced etherification to construct a bridged structure.

The first total synthesis of phomopsol B has been achieved in a racemic form. The synthesis comprises a deacetylative cyclization to construct a bicyclic skeleton followed by primary alcohol-assisted dihydroxylation, ether cyclization to construct a dioxabicyclo [3.2.1] skeleton and γ-lactone formation based on oxidation by TEMPO.